A novel vaccine against Crimean-Congo Haemorrhagic Fever protects 100% of animals against lethal challenge in a mouse model

PLoS One. 2014 Mar 12;9(3):e91516. doi: 10.1371/journal.pone.0091516. eCollection 2014.

Abstract

Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal. There is no approved vaccine available, and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus glycoproteins. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • DNA, Recombinant / genetics
  • Disease Models, Animal
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / immunology
  • Hemorrhagic Fever Virus, Crimean-Congo / immunology
  • Hemorrhagic Fever Virus, Crimean-Congo / physiology
  • Hemorrhagic Fever, Crimean / immunology
  • Hemorrhagic Fever, Crimean / metabolism
  • Hemorrhagic Fever, Crimean / pathology
  • Hemorrhagic Fever, Crimean / prevention & control*
  • Immunity, Cellular
  • Immunity, Humoral
  • Mice
  • Plasmids / genetics
  • Receptor, Interferon alpha-beta / deficiency
  • Receptors, Interferon / deficiency
  • Viral Load
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • DNA, Recombinant
  • Glycoproteins
  • Receptors, Interferon
  • Viral Proteins
  • Viral Vaccines
  • interferon receptor, type II
  • Receptor, Interferon alpha-beta

Grants and funding

This work was funded by the Health Protection Agency (subsequently part of Public Health England) of the United Kingdom. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.